A recent study has found that fractional doses of the 13-valent pneumococcal conjugate vaccine (PCV13) could offer a cost-effective solution for immunizing infants, particularly in under-resourced regions. The research, conducted in Kenya, demonstrated that a 40% fractional dose of PCV13 (Pfizer) was non-inferior to a full dose in terms of immunogenicity. This finding could have significant implications for sustaining vaccination programs in low- and middle-income countries where the cost of pneumococcal vaccines remains a major barrier.
Immunogenicity of Fractional Doses
The study, led by Katherine Gallagher, PhD, from the London School of Hygiene & Tropical Medicine, compared the immunogenicity of full doses, 40% fractional doses, and 20% fractional doses of both PCV13 and the 10-valent pneumococcal conjugate vaccine (PCV10, GSK). Over 2,000 infants were randomly assigned to one of six treatment conditions, with a seventh group receiving a full dose of PCV10 as three primary doses without a booster. The primary measure of immunogenicity was serum IgG to vaccine-type capsular polysaccharides, assessed four weeks after the third dose.
The investigators reported that the 40% fractional dose of PCV13 met the noninferiority criterion for 12 of 13 serotypes after the primary series and for all 13 serotypes after the booster. However, neither the 20% dose of PCV13 nor the 40% or 20% fractional doses of PCV10 met that threshold. Vaccine serotype-type carriage prevalence was similar across the PCV13 groups at 9 and 18 months of age.
Cost Implications and Vaccine Access
Gallagher and her colleagues highlight that the $2-3 cost per dose of pneumococcal vaccine, given in a three-dose series, is the most expensive component of the routine immunization schedule in many of the 47 WHO-designated low- and lower-middle-income countries. "The sustainability of the pneumococcal vaccine program is in question in countries that are transitioning out of Gavi (the Vaccine Alliance) support and taking on the full cost of procuring the vaccine," they noted.
For middle-income countries ineligible for Gavi support, reducing the cost of the pneumococcal conjugate vaccine may enable vaccine introduction in areas where it is currently unaffordable. The trial findings support off-label use of the 40% fractional PCV13 dosing to help sustain pneumococcal vaccine immunization programs.
Serum IgG as a Marker for Vaccine Effectiveness
Serum IgG has traditionally been used as a marker for vaccine effectiveness. Gallagher explained that the first trials of PCVs measured serum IgG and disease endpoints, generating a correlate of protection among infants—a threshold of IgG above which the risk of invasive pneumococcal disease (IPD) was minimal. However, she also pointed out that protection against pneumococcal carriage and invasion of pneumococci into sterile sites is a complex biological process.
"It is likely to be a surrogate marker for other immune actors that are active at the mucosa. As such, as newer PCVs are licensed and elicit lower IgG, but non-inferior responses, it is unclear whether these PCVs will be as protective or will have attenuated protection," Gallagher suggested.
Future Directions
Gallagher hopes that the findings, along with lower-cost full-dose products from alternative sources such as the Serum Institute of India (SII), will prompt the principle vaccine manufacturers to further reduce their prices for under-resourced regions. She believes this would be easier for them than changing their manufacturing volumes to meet the lower demand if fractional doses were implemented across multiple countries.
